Teratogenic effects in mouse fetuses subjected to the concurrent in utero exposure to miconazole and metronidazole.
The potential interactivity of the antimicrobials miconazole and metronidazole in the induction of teratogenic effects was investigated in the present study. Drugs were injected at 60 mg/kg either individually or in combination to pregnant mice on gestation day (GD) 8, 9, or 10. Teratological assessments were carried out on GD 18. A potent teratogenic interaction resulted from miconazole-metronidazole co-administration, causing an increment in axial skeletal defects incidence. While, the individual exposure to miconazole or metronidazole produced axial skeletal defects at frequencies that did not exceed 5.6% in the various treatment groups, the percentage of fetuses with malformed skeleton reached 26% after co-exposure on GD 8 or GD 9. No significant synergism was noted when drugs were co-administered on GD 10. This study shows that a teratogenic interaction can result from miconazole-metronidazole concomitant exposure.
Tiboni
Gian Mario
GM
Sezione di Ostetricia e Ginecologia, Dipartimento di Medicina e Scienze dell'Invecchiamento, Facoltà di Medicina e Chirurgia, Università "G. d'Annunzio" di Chieti-Pescara, Italy. tiboni@unich.it
Marotta
Francesca
F
Castigliego
Anna Pia
AP
D000014:Abnormalities, Drug-Induced; D000818:Animals; D000890:Anti-Infective Agents / Q000633:toxicity*; D001842:Bone and Bones / Q000002:abnormalities; D004357:Drug Synergism; D005260:Female; D008795:Metronidazole / Q000633:toxicity*; D051379:Mice; D008813:Mice, Inbred ICR; D008825:Miconazole / Q000633:toxicity*; D011247:Pregnancy
D000890:Anti-Infective Agents; D008795:Metronidazole; D008825:Miconazole